RESUMEN
RATIONALE: Individuals with COPD have airflow obstruction and maldistribution of ventilation. For those living at high altitude, any gas exchange abnormality is compounded by reduced partial pressures of inspired oxygen. OBJECTIVES: Does residence at higher-altitude exposure affect COPD outcomes, including lung function, imaging characteristics, symptoms, health status, functional exercise capacity, exacerbations, or mortality? METHODS: From the SPIROMICS cohort, we identified individuals with COPD living below 1,000 ft (305 m) elevation (n= 1,367) versus above 4,000 ft (1,219 m) elevation (n= 288). Multivariable regression models were used to evaluate associations of exposure to high altitude with COPD-related outcomes. MEASUREMENTS AND MAIN RESULTS: Living at higher altitude was associated with reduced functional exercise capacity as defined by 6MWD (-32.3 m, (-55.7 to -28.6)). There were no differences in patient-reported outcomes as defined by symptoms (CAT, mMRC), or health status (SGRQ). Higher altitude was not associated with a different rate of FEV1 decline. Higher altitude was associated with lower odds of severe exacerbations (IRR 0.65, (0.46 to 0.90)). There were no differences in small airway disease, air trapping, or emphysema. In longitudinal analyses, higher altitude was associated with increased mortality (HR 1.25, (1.0 to 1.55)); however, this association was no longer significant when accounting for air pollution. CONCLUSIONS: Chronic altitude exposure is associated with reduced functional exercise capacity in individuals with COPD, but this did not translate into differences in symptoms or health status. Additionally, chronic high-altitude exposure did not affect progression of disease as defined by longitudinal changes in spirometry.
RESUMEN
PURPOSE OF REVIEW: Every type of dry powder inhaler (DPI) device has its own intrinsic resistance. A patient's inspiratory effort produces a pressure drop that determines the inspiratory flow, depending on the inhaler's specific internal resistance. Optimal peak inspiratory flow (PIF) is needed for effective release of dry powder, disaggregation of drug-carrier agglomerates, and optimal deposition of respirable drug particles, particularly generation of a high fine-particle fraction to reach the small airways of the lungs. However, standardized recommendations for PIF measurements are lacking and instructions appeared vague in many instances. RECENT FINDINGS: Suboptimal PIFs are common in outpatient chronic obstructive pulmonary disease (COPD) patients and during acute exacerbations of COPD, and are associated with increased healthcare resource utilization. There is significant variation in the results of studies which is in part related to different definitions of optimal flow rates, and considerable variation in how PIF is measured in clinical and real-life studies. SUMMARY: Standardization of technique will facilitate comparisons among studies. Specific recommendations for PIF measurement have been proposed to standardize the process and better ensure accurate and reliable PIF values in clinical trials and clinical practice. Clinicians can then select and personalize the most appropriate inhaler for their patients and help them achieve the optimal PIF needed for effective drug dispersion.
Asunto(s)
Inhaladores de Polvo Seco , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Pulmón , Administración por InhalaciónRESUMEN
There is irrefutable evidence that germline BRCA1-associated protein 1 gene (BAP1) mutations contribute to malignant mesothelioma (MM) susceptibility. However, BAP1 mutations are not found in all cases with evidence of familial MM or in other high-risk cancer families affected by various cancers, including MM. The goal of this study was to use whole genome sequencing (WGS) to determine the frequency and types of germline gene variants occurring in 12 MM patients who were selected from a series of 141 asbestos-exposed MM patients with a family history of cancer but without a germline BAP1 mutation. WGS was also performed on two MM cases, a proband and sibling, from a previously reported family with multiple cases of MM without the inheritance of a predisposing BAP1 mutation. Altogether, germline DNA sequencing variants were identified in 21 cancer-related genes in 10 of the 13 probands. Germline indel, splice site and missense mutations and two large deletions were identified. Among the 13 MM index cases, 6 (46%) exhibited one or more predicted pathogenic mutations. Affected genes encode proteins involved in DNA repair (ATM, ATR, BRCA2, BRIP1, CHEK2, MLH3, MUTYH, POLE, POLE4, POLQ and XRCC1), chromatin modification (ARID1B, DNMT3A, JARID2 and SETD1B) or other cellular pathways: leucine-rich repeat kinase 2 gene (LRRK2) (two cases) and MSH4. Notably, somatic truncating mutation or deletions of LRRK2 were occasionally found in MMs in The Cancer Genome Atlas, and the expression of LRRK2 was undetectable or downregulated in a majority of primary MMs and MM cell lines we examined, implying that loss of LRRK2 expression is a newly recognized tumor suppressor alteration in MM.
Asunto(s)
Predisposición Genética a la Enfermedad , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/genética , Mesotelioma Maligno/genética , Proteínas Supresoras de Tumor/genética , Ubiquitina Tiolesterasa/genética , Adulto , Humanos , Masculino , Factores de RiesgoRESUMEN
Importance: People who smoked cigarettes may experience respiratory symptoms without spirometric airflow obstruction. These individuals are typically excluded from chronic obstructive pulmonary disease (COPD) trials and lack evidence-based therapies. Objective: To define the natural history of persons with tobacco exposure and preserved spirometry (TEPS) and symptoms (symptomatic TEPS). Design, Setting, and Participants: SPIROMICS II was an extension of SPIROMICS I, a multicenter study of persons aged 40 to 80 years who smoked cigarettes (>20 pack-years) with or without COPD and controls without tobacco exposure or airflow obstruction. Participants were enrolled in SPIROMICS I and II from November 10, 2010, through July 31, 2015, and followed up through July 31, 2021. Exposures: Participants in SPIROMICS I underwent spirometry, 6-minute walk distance testing, assessment of respiratory symptoms, and computed tomography of the chest at yearly visits for 3 to 4 years. Participants in SPIROMICS II had 1 additional in-person visit 5 to 7 years after enrollment in SPIROMICS I. Respiratory symptoms were assessed with the COPD Assessment Test (range, 0 to 40; higher scores indicate more severe symptoms). Participants with symptomatic TEPS had normal spirometry (postbronchodilator ratio of forced expiratory volume in the first second [FEV1] to forced vital capacity >0.70) and COPD Assessment Test scores of 10 or greater. Participants with asymptomatic TEPS had normal spirometry and COPD Assessment Test scores of less than 10. Patient-reported respiratory symptoms and exacerbations were assessed every 4 months via phone calls. Main Outcomes and Measures: The primary outcome was assessment for accelerated decline in lung function (FEV1) in participants with symptomatic TEPS vs asymptomatic TEPS. Secondary outcomes included development of COPD defined by spirometry, respiratory symptoms, rates of respiratory exacerbations, and progression of computed tomographic-defined airway wall thickening or emphysema. Results: Of 1397 study participants, 226 had symptomatic TEPS (mean age, 60.1 [SD, 9.8] years; 134 were women [59%]) and 269 had asymptomatic TEPS (mean age, 63.1 [SD, 9.1] years; 134 were women [50%]). At a median follow-up of 5.76 years, the decline in FEV1 was -31.3 mL/y for participants with symptomatic TEPS vs -38.8 mL/y for those with asymptomatic TEPS (between-group difference, -7.5 mL/y [95% CI, -16.6 to 1.6 mL/y]). The cumulative incidence of COPD was 33.0% among participants with symptomatic TEPS vs 31.6% among those with asymptomatic TEPS (hazard ratio, 1.05 [95% CI, 0.76 to 1.46]). Participants with symptomatic TEPS had significantly more respiratory exacerbations than those with asymptomatic TEPS (0.23 vs 0.08 exacerbations per person-year, respectively; rate ratio, 2.38 [95% CI, 1.71 to 3.31], P < .001). Conclusions and Relevance: Participants with symptomatic TEPS did not have accelerated rates of decline in FEV1 or increased incidence of COPD vs those with asymptomatic TEPS, but participants with symptomatic TEPS did experience significantly more respiratory exacerbations over a median follow-up of 5.8 years.
Asunto(s)
Fumar Cigarrillos , Enfermedades Pulmonares , Espirometría , Femenino , Humanos , Masculino , Persona de Mediana Edad , Progresión de la Enfermedad , Estudios de Seguimiento , Volumen Espiratorio Forzado , Pulmón/diagnóstico por imagen , Pulmón/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Enfermedad Pulmonar Obstructiva Crónica/etiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Capacidad Vital , Estudios Longitudinales , Fumar Cigarrillos/efectos adversos , Fumar Cigarrillos/fisiopatología , Enfermedades Pulmonares/diagnóstico por imagen , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/fisiopatología , Pruebas de Función RespiratoriaRESUMEN
Background: Noninvasive ventilation (NIV) is used for patients with chronic obstructive pulmonary disease (COPD) and chronic hypercapnia. However, evidence for clinical efficacy and optimal management of therapy is limited.Target Audience: Patients with COPD, clinicians who care for them, and policy makers.Methods: We summarized evidence addressing five PICO (patients, intervention, comparator, and outcome) questions. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to evaluate the certainty in evidence and generate actionable recommendations. Recommendations were formulated by a panel of pulmonary and sleep physicians, respiratory therapists, and methodologists using the Evidence-to-Decision framework.Recommendations:1) We suggest the use of nocturnal NIV in addition to usual care for patients with chronic stable hypercapnic COPD (conditional recommendation, moderate certainty); 2) we suggest that patients with chronic stable hypercapnic COPD undergo screening for obstructive sleep apnea before initiation of long-term NIV (conditional recommendation, very low certainty); 3) we suggest not initiating long-term NIV during an admission for acute-on-chronic hypercapnic respiratory failure, favoring instead reassessment for NIV at 2-4 weeks after resolution (conditional recommendation, low certainty); 4) we suggest not using an in-laboratory overnight polysomnogram to titrate NIV in patients with chronic stable hypercapnic COPD who are initiating NIV (conditional recommendation, very low certainty); and 5) we suggest NIV with targeted normalization of PaCO2 in patients with hypercapnic COPD on long-term NIV (conditional recommendation, low certainty).Conclusions: This expert panel provides evidence-based recommendations addressing the use of NIV in patients with COPD and chronic stable hypercapnic respiratory failure.
Asunto(s)
Hipercapnia/terapia , Ventilación no Invasiva/normas , Enfermedad Pulmonar Obstructiva Crónica/terapia , Enfermedad Crónica , Humanos , Hipercapnia/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Factores de TiempoRESUMEN
Bronchodilator reversibility occurs in patients with COPD. Pooled analysis of two 12-week, placebo-controlled randomised studies (FLIGHT1 [NCT01727141]; FLIGHT2 [NCT01712516]) assessed the effect of bronchodilator reversibility on lung function, patient-reported outcomes, and safety in 2,043 patients with moderate-to-severe COPD treated with indacaterol/glycopyrrolate (IND/GLY) 27.5/15.6 µg twice daily. Reversibility was defined as post-bronchodilator increase in forced expiratory volume in one second (FEV1) of ≥12% and ≥0.200 L. Overall, mean reversibility (mean post-bronchodilator FEV1 increase) was 22.8%, and 54.5% of patients met reversibility criteria. IND/GLY resulted in significant (p < 0.05) placebo-adjusted improvements from baseline at Week 12 in reversible and non-reversible patients in FEV1 area under the curve from 0 to 12 hours (0.308 L and 0.170 L, respectively), trough FEV1 (0.260 L and 0.174 L), St. George's Respiratory Questionnaire total score (-6.3 and -3.5), COPD Assessment Test total score (-2.3 and -1.2), daily rescue medication use (-1.52 and -0.79), and daily total symptom score (-0.86 and -0.63); Transition Dyspnoea Index focal score also showed improvements (1.93 and 1.29) at Week 12, irrespective of reversibility status. Improvements in lung function and rescue medication use were significantly (p < 0.05) greater in IND/GLY patients in the reversible subgroup compared with the non-reversible subgroup. The safety profile was similar across treatment groups and reversibility subgroups. Overall, treatment with IND/GLY led to significant improvements in lung function and PROs in patients with moderate-to-severe COPD, regardless of reversibility status, with greater improvements in the reversible subgroup. Safety profile was not affected by reversibility status.
Asunto(s)
Glicopirrolato/uso terapéutico , Indanos/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Quinolonas/uso terapéutico , Fármacos del Sistema Respiratorio/uso terapéutico , Adulto , Anciano , Broncodilatadores , Esquema de Medicación , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
OBJECTIVE: To assess relationships between obstructive lung diseases, respiratory symptoms, and comorbidities by gender. METHODS: Data from 12 594 adult respondents to the 2012 South Carolina Behavioral Risk Factor Surveillance System telephone survey were used. Five categories of chronic obstructive airway disease (OAD) were defined: former asthma only, current asthma only, chronic obstructive pulmonary disease (COPD) only, asthma-COPD overlap syndrome (ACOS), and none. Associations of these categories with respiratory symptoms (frequent productive cough, shortness of breath, and impaired physical activities due to breathing problems), overall health, and comorbidities were assessed using multivariable logistic regression for men and women. RESULTS: Overall, 16.2% of men and 18.7% of women reported a physician diagnosis of COPD and/or asthma. Former asthma only was higher among men than women (4.9% vs. 3.2%, t-test p = 0.008). Current asthma only was more prevalent among women than men (7.2% vs. 4.7%, p < 0.001), as was ACOS (4.0% vs. 2.2%, p < 0.001). Having COPD only did not differ between women (4.3%) and men (4.4%). Adults with ACOS were most likely to report the 3 respiratory symptoms. COPD only and ACOS were associated with higher likelihoods of poor health and most comorbidities for men and women. Current asthma only was also associated with these outcomes among women, but not among men. CONCLUSIONS: In this large population-based sample, women were more likely than men to report ACOS and current asthma, but not COPD alone. Gender differences were evident between the OAD groups in sociodemographic characteristics, respiratory symptoms, and comorbidities, as well as overall health.
Asunto(s)
Asma/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Asma/etnología , Sistema de Vigilancia de Factor de Riesgo Conductual , Índice de Masa Corporal , Comorbilidad , Femenino , Estado de Salud , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Prevalencia , Enfermedad Pulmonar Obstructiva Crónica/etnología , Factores de Riesgo , Factores Sexuales , Fumar/epidemiología , Factores Socioeconómicos , South Carolina/epidemiología , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Chronic lung disease is common and often under-diagnosed. METHODS: To test a simple rule for conducting spirometry we reviewed spirograms from two populations, occupational medicine evaluations (OME) conducted by Saint Louis and Wake Forest Universities at 3 sites (n = 3260, mean age 64.14 years, 95 % CI 58.94-69.34, 97 % men) and conducted by Wake Forest University preop clinic (POC) at one site (n = 845, mean age 62.10 years, 95 % CI 50.46-73.74, 57 % men). This retrospective review of database information that the first author collected prospectively identified rates, types, sensitivity, specificity and positive and negative predictive value for lung function abnormalities and associated mortality rate found when conducting spirometry based on the 20/40 rule (≥20 years of smoking in those aged ≥ 40 years) in the OME population. To determine the reproducibility of the 20/40 rule for conducting spirometry, the rule was applied to the POC population. RESULTS: A lung function abnormality was found in 74 % of the OME population and 67 % of the POC population. Sensitivity of the rule was 85 % for an obstructive pattern and 77 % for any abnormality on spirometry. Positive and negative predictive values of the rule for a spirometric abnormality were 74 and 55 %, respectively. Patients with an obstructive pattern were at greater risk of coronary heart disease (odds ratio (OR) 1.39 [confidence interval (CI) 1.00-1.93] vs. normal) and death (hazard ratio (HR) 1.53, 95 % CI 1.20-1.84) than subjects with normal spirometry. Restricted spirometry patterns were also associated with greater risk of coronary disease (odds ratio (OR) 1.7 [CI 1.23-2.35]) and death (Hazard ratio 1.40, 95 % CI 1.08-1.72). CONCLUSIONS: Smokers (≥ 20 pack years) age ≥ 40 years are at an increased risk for lung function abnormalities and those abnormalities are associated with greater presence of coronary heart disease and increased all-cause mortality. Use of the 20/40 rule could provide a simple method to enhance selection of candidates for spirometry evaluation in the primary care setting.
Asunto(s)
Algoritmos , Enfermedad Coronaria/epidemiología , Selección de Paciente , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Fumar , Espirometría , Factores de Edad , Anciano , Comorbilidad , Enfermedad Coronaria/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Reproducibilidad de los Resultados , Estudios Retrospectivos , Autoinforme , Fumar/fisiopatología , Tasa de Supervivencia , Factores de TiempoRESUMEN
UNLABELLED: The Behavioral Risk Factor Surveillance System (BRFSS) survey is used to estimate chronic obstructive pulmonary disease (COPD) prevalence and could be expanded to describe respiratory symptoms in the general population and to characterize persons with or at high risk for the disease. Tobacco duration and respiratory symptom questions were added to the 2012 South Carolina BRFSS. Data concerning sociodemographics, chronic illnesses, health behaviors, and respiratory symptoms were collected in 9438 adults ≥ 35 years-old. Respondents were categorized as having COPD, high risk, or low risk for the disease. High risk was defined as no self-reported COPD, ≥ 10 years' tobacco use, and ≥ 1 respiratory symptom (frequent productive cough or shortness of breath (SOB), or breathing problems affecting activities). Prevalence of self-reported and high-risk COPD were 9.1% and 8.0%, respectively. Overall, 17.3%, 10.6%, and 5.2% of all respondents reported activities limited by breathing problems, frequent productive cough, and frequent SOB, respectively. The high-risk group was more likely than the COPD group to report a productive cough and breathing problems limiting activities as well as being current smokers, male, and African-American. Health impairment was more severe in the COPD than the high-risk group, and both were worse than the low-risk group. CONCLUSIONS: Persons at high risk for COPD share many, but not all, of the characteristics of persons diagnosed with the disease. Additional questions addressing smoking duration and respiratory symptoms in the BRFSS identifies groups at high risk for having or developing COPD who may benefit from smoking cessation and case-finding interventions.
Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Adulto , Anciano , Sistema de Vigilancia de Factor de Riesgo Conductual , Femenino , Conductas Relacionadas con la Salud , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Medición de Riesgo , Autoinforme , Fumar , Factores Socioeconómicos , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Inhaled long-acting beta2 agonists used alone and in combination with an inhaled corticosteroid reduce the risk of exacerbations in patients with stable COPD. However, the relative efficacy of these agents in preventing recurrent exacerbations in those recovering from an initial episode is not known. This study compared the rate of COPD exacerbations over the 26 weeks after an initial exacerbation in patients receiving the combination of fluticasone propionate and salmeterol (FP/SAL) or SAL alone. METHODS: Patients (n = 639) aged ≥40 years were randomized to either twice-daily inhaled FP/SAL 250/50 µg or SAL 50 µg. Primary, and secondary, endpoints were rates of recurrent severe, and moderate/severe, exacerbations of COPD. Lung function, health outcomes and levels of biomarkers of systemic inflammation were also assessed. RESULTS: There was no statistically significant treatment difference in rates of recurrent severe exacerbations (treatment ratio 0.92 [95% CI: 0.58, 1.45]) and moderate/severe exacerbations (0.82 [0.64, 1.06]) between FP/SAL and SAL in the intent-to-treat population. Pre-dose morning FEV1 change from baseline was greater (0.10 L [0.04, 0.16]) with FP/SAL than SAL. No treatment difference was seen for other endpoints including patient-reported health outcomes and biomarker levels for the full cohort. CONCLUSIONS: No significant treatment difference between FP/SAL and SAL was seen in COPD exacerbation recurrence for the complete cohort. Treatment benefit with FP/SAL over SAL (treatment ratio 0.68 [0.47, 0.97]) was seen in patients having FEV1 ≥ 30% and prior exposure to ICS. No unexpected safety issues were identified with either treatment. Patients with the most severe COPD may be more refractory to treatment. TRIAL REGISTRATION: ClinicalTrials.gov (identifier NCT01110200). This study was funded by GlaxoSmithKline (study number ADC113874).
Asunto(s)
Albuterol/análogos & derivados , Androstadienos/administración & dosificación , Broncodilatadores/administración & dosificación , Progresión de la Enfermedad , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Administración por Inhalación , Anciano , Albuterol/administración & dosificación , Método Doble Ciego , Combinación de Medicamentos , Femenino , Combinación Fluticasona-Salmeterol , Humanos , Masculino , Persona de Mediana Edad , Xinafoato de SalmeterolRESUMEN
UNLABELLED: Abstract Background: Persons with chronic obstructive pulmonary disease (COPD) and/or asthma have great risk for morbidity. There has been sparse state-specific surveillance data to estimate the impact of COPD or COPD with concomitant asthma (overlap syndrome) on health-related impairment. METHODS: The North Carolina (NC) Behavioral Risk Factor Surveillance System (BRFSS) was used to assess relationships between COPD and asthma with health impairment indicators. Five categories [COPD, current asthma, former asthma, overlap syndrome, and neither] were defined for 24,073 respondents. Associations of these categories with health impairments (physical or mental disability, use of special equipment, mental or physical distress) and with co-morbidities (diabetes, coronary heart disease, stroke, arthritis, and high blood pressure) were assessed. RESULTS: Fifteen percent of NC adults reported a COPD and/or asthma history. The overall age-adjusted prevalence of any self-reported COPD and current asthma were 5.6% and 7.6%, respectively; 2.4% reported both. In multivariable analyses, adults with overlap syndrome, current asthma only, and COPD only were twice as likely as those with neither disease to report health impairments (p < 0.05). Compared to those with neither disease, adults with overlap syndrome and COPD were more likely to have co-morbidities (p < 0.05). The prevalence of the five co-morbid conditions was highest in overlap syndrome; comparisons with the other groups were significant (p < 0.05) only for diabetes, stroke, and arthritis. CONCLUSIONS: The BRFSS demonstrates different levels of health impairment among persons with COPD, asthma, overlap syndrome, and those with neither disease. Persons reporting overlap syndrome had the most impairment and highest prevalence of co-morbidities.
Asunto(s)
Asma/epidemiología , Estado de Salud , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Actividades Cotidianas , Adolescente , Adulto , Anciano , Artritis/epidemiología , Asma/psicología , Sistema de Vigilancia de Factor de Riesgo Conductual , Comorbilidad , Enfermedad Coronaria/epidemiología , Diabetes Mellitus/epidemiología , Femenino , Humanos , Hipertensión/epidemiología , Masculino , Salud Mental/estadística & datos numéricos , Persona de Mediana Edad , North Carolina/epidemiología , Prevalencia , Enfermedad Pulmonar Obstructiva Crónica/psicología , Dispositivos de Autoayuda/estadística & datos numéricos , Fumar/epidemiología , Factores Socioeconómicos , Accidente Cerebrovascular/epidemiología , Adulto JovenRESUMEN
INTRODUCTION: The selection of inhaler device is of critical importance in chronic obstructive pulmonary disease (COPD) as the interaction between a patient's inhalation profile and the aerosol characteristics of an inhaler can affect drug delivery and lung deposition. This study assessed the in vitro aerosol characteristics of inhaler devices approved for the treatment of COPD, including a soft mist inhaler (SMI), pressurized metered-dose inhalers (pMDIs), and dry powder inhalers (DPIs). METHODS: High-speed video recording was used to visualize and measure aerosol velocity and spray duration for nine different inhalers (one SMI, three pMDIs, and five DPIs), each containing dual or triple fixed-dose combinations of long-acting muscarinic receptor antagonists and long-acting ß2-agonists, with or without an inhaled corticosteroid. Measurements were taken in triplicate at experimental flow rates of 30, 60, and 90 l/min. Optimal flow rates were defined based on pharmacopoeial testing requirements: 30 l/min for pMDIs and SMIs, and the rate achieving a 4-kPa pressure drop against internal inhaler resistance for DPIs. Comparison of aerosol plumes was based on the experimental flow rates closest to the optimal flow rates. RESULTS: The Respimat SMI had the slowest plume velocity (0.99 m/s) and longest spray duration (1447 ms) compared with pMDIs (velocity: 3.65-5.09 m/s; duration: 227-270 ms) and DPIs (velocity: 1.43-4.60 m/s; duration: 60-757 ms). With increasing flow rates, SMI aerosol duration was unaffected, but velocity increased (maximum 2.63 m/s), pMDI aerosol velocity and duration were unaffected, and DPI aerosol velocity tended to increase, with a more variable impact on duration. CONCLUSIONS: Aerosol characteristics (velocity and duration of aerosol plume) vary by inhaler type. Plume velocity was lower and spray duration longer for the SMI compared with pMDIs and DPIs. Increasing experimental flow rate was associated with faster plume velocity for DPIs and the SMI, with no or variable impact on plume duration, whereas pMDI aerosol velocity and duration were unaffected by increasing flow rate.
RESUMEN
Introduction: Many patients with chronic obstructive pulmonary disease (COPD) may derive inadequate benefit from dry powder inhalers (DPIs) because of suboptimal peak inspiratory flow (sPIF). Objectives: To assess the clinical burden of COPD by characterizing the clinical characteristics of participants with sPIF against medium-low resistance DPIs versus those with optimal PIF (oPIF) from two phase 3 clinical trials. Methods: Baseline data were collected from two randomized, controlled, phase 3 trials (NCT03095456; NCT02518139) in participants with moderate-to-severe COPD. oPIF (60 L/min) against the medium-low resistance DPIs was used as the threshold for defining the PIF subgroups (<60 L/min (sPIF) vs ≥60 L/min (oPIF)). Results: Most participants included in this analysis were White (92%) and male (63%); the mean (range) age was 65 (43-87) years. Participants with sPIF had significantly greater dyspnea than those with oPIF as measured using the modified Medical Research Council scoring (mean (95% CI): 2.1 (2.0-2.2) vs 1.6 (1.4-1.7); P < 0.001) and baseline dyspnea index (mean (95% CI): 5.1 (4.9-5.4) vs 6.1 (5.8-6.3); P < 0.001). Based on COPD Assessment Test scores, participants with sPIF had a higher COPD symptom burden than those with oPIF (mean (95% CI): 21.5 (19.7-23.3) vs 19.5 (18.6-20.4); P = 0.05). Conclusion: In these trials, participants with COPD who had sPIF against the medium-low resistance DPIs had more dyspnea and worse health status than those with oPIF. These results demonstrate that sPIF is associated with a higher clinical burden as measured by patient-reported outcomes.
Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Administración por Inhalación , Inhaladores de Polvo Seco , Disnea/etiología , Carga Sintomática , Femenino , Adulto , Persona de Mediana Edad , Ensayos Clínicos Fase III como Asunto , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Nebulizers are used commonly for inhaled drug delivery. Because they deliver medication through aerosol generation, clarification is needed on what constitutes safe aerosol delivery in infectious respiratory disease settings. The COVID-19 pandemic highlighted the importance of understanding the safety and potential risks of aerosol-generating procedures. However, evidence supporting the increased risk of disease transmission with nebulized treatments is inconclusive, and inconsistent guidelines and differing opinions have left uncertainty regarding their use. Many clinicians opt for alternative devices, but this practice could impact outcomes negatively, especially for patients who may not derive full treatment benefit from handheld inhalers. Therefore, it is prudent to develop strategies that can be used during nebulized treatment to minimize the emission of fugitive aerosols, these comprising bioaerosols exhaled by infected individuals and medical aerosols generated by the device that also may be contaminated. This is particularly relevant for patient care in the context of a highly transmissible virus. RESEARCH QUESTION: How can potential risks of infections during nebulization be mitigated? STUDY DESIGN AND METHODS: The COPD Foundation Nebulizer Consortium (CNC) was formed in 2020 to address uncertainties surrounding administration of nebulized medication. The CNC is an international, multidisciplinary collaboration of patient advocates, pulmonary physicians, critical care physicians, respiratory therapists, clinical scientists, and pharmacists from research centers, medical centers, professional societies, industry, and government agencies. The CNC developed this expert guidance to inform the safe use of nebulized therapies for patients and providers and to answer key questions surrounding medication delivery with nebulizers during pandemics or when exposure to common respiratory pathogens is anticipated. RESULTS: CNC members reviewed literature and guidelines regarding nebulization and developed two sets of guidance statements: one for the health care setting and one for the home environment. INTERPRETATION: Future studies need to explore the risk of disease transmission with fugitive aerosols associated with different nebulizer types in real patient care situations and to evaluate the effectiveness of mitigation strategies.
Asunto(s)
COVID-19 , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Administración por Inhalación , Pandemias/prevención & control , Aerosoles y Gotitas Respiratorias , Nebulizadores y Vaporizadores , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , BroncodilatadoresRESUMEN
The biological mechanisms leading some tobacco-exposed individuals to develop early-stage chronic obstructive pulmonary disease (COPD) are poorly understood. This knowledge gap hampers development of disease-modifying agents for this prevalent condition. Accord-ingly, with National Heart, Lung and Blood Institute support, we initiated the SPIROMICS Study of Early COPD Progression (SOURCE), a multicenter observational cohort study of younger individuals with a history of cigarette smoking and thus at-risk for, or with, early-stage COPD. Our overall objectives are to identify those who will develop COPD earlier in life, characterize them thoroughly, and by contrasting them to those not developing COPD, define mechanisms of disease progression. SOURCE utilizes the established SPIROMICS clinical network. Its goal is to enroll n=649 participants, ages 30-55 years, all races/ethnicities, with ≥10 pack-years cigarette smoking, in either Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups 0-2 or with Preserved Ratio Impaired Spirometry (PRISm); and an additional n=40 never-smoker controls. Participants undergo baseline and three-year follow-up visits, each including high-resolution computed tomography; respiratory oscillometry and spirometry (pre- and post-bronchodilator administration), exhaled breath condensate (baseline only); and extensive biospecimen collection, including sputum induction. Symptoms, interim healthcare utilization, and exacerbations are captured every six months via follow-up phone calls. An embedded bronchoscopy sub-study involving n=100 participants (including all never-smokers) will allow collection of lower airway samples for genetic, epigenetic, genomic, immunological, microbiome, mucin analyses, and basal cell culture. SOURCE should provide novel insights into the natural history of lung disease in younger individuals with a smoking history, and its biological basis.
RESUMEN
Deletions on human chromosome 8p22-23 in prostate cancer cells and linkage studies in families affected with hereditary prostate cancer (HPC) have implicated this region in the development of prostate cancer. The macrophage scavenger receptor 1 gene (MSR1, also known as SR-A) is located at 8p22 and functions in several processes proposed to be relevant to prostate carcinogenesis. Here we report the results of genetic analyses that indicate that mutations in MSR1 may be associated with risk of prostate cancer. Among families affected with HPC, we identified six rare missense mutations and one nonsense mutation in MSR1. A family-based linkage and association test indicated that these mutations co-segregate with prostate cancer (P = 0.0007). In addition, among men of European descent, MSR1 mutations were detected in 4.4% of individuals affected with non-HPC as compared with 0.8% of unaffected men (P = 0.009). Among African American men, these values were 12.5% and 1.8%, respectively (P = 0.01). These results show that MSR1 may be important in susceptibility to prostate cancer in men of both African American and European descent.
Asunto(s)
Variación Genética , Mutación , Neoplasias de la Próstata/genética , Receptores Inmunológicos/genética , Anciano , Sustitución de Aminoácidos , Población Negra/genética , Análisis Mutacional de ADN , Femenino , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Humanos , Macrófagos/metabolismo , Masculino , Persona de Mediana Edad , Linaje , Neoplasias de la Próstata/etiología , Estructura Terciaria de Proteína , Receptores Inmunológicos/metabolismo , Receptores Depuradores , Receptores Depuradores de Clase A , Población Blanca/genéticaRESUMEN
BACKGROUND: Replicate, 12-week, phase 3 trials (0126 and 0127) of once-daily nebulized revefenacin 175 µg vs placebo demonstrated significant bronchodilation and improvements in health status in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). This post hoc analysis evaluated improvement in patient-reported outcomes (PROs), including the St. George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT), and Clinical COPD Questionnaire (CCQ) in both women and men. METHODS: Participants were pooled from the two 12-week studies (411 [51%] women and 401 [49%] men). Changes in PROs were assessed overall and separately in men and women. RESULTS: Revefenacin improved SGRQ and CAT total scores from baseline in both studies; improvement in CCQ total score reached significance only in 0126. In pooled data, a greater proportion of patients achieved clinically meaningful response in SGRQ score (≥4-unit decrease from baseline) with revefenacin vs placebo (odds ratio, 1.5; 95% confidence interval, 1.1-2.1; P = 0.012). Clinically meaningful responses were also seen in CAT (≥2-unit decrease from baseline) and CCQ (≥0.4-unit decrease from baseline) scores with revefenacin vs placebo. When stratified by sex, improvements from baseline in SGRQ, CAT, and CCQ scores following revefenacin vs placebo reached statistical significance only in women. CONCLUSIONS: Maintenance treatment with revefenacin improved health status in patients with moderate to very severe COPD; however, the effect was more pronounced for women than men. CLINICALTRIALS: GOV: NCT02459080; NCT02512510.
Asunto(s)
Antagonistas Muscarínicos , Enfermedad Pulmonar Obstructiva Crónica , Femenino , Humanos , Masculino , Benzamidas , Broncodilatadores/uso terapéutico , Volumen Espiratorio Forzado , Estado de SaludRESUMEN
Background: Limited data are available regarding marijuana smoking's impact on the development or progression of chronic obstructive pulmonary disease (COPD) in middle-aged or older adults with a variable history of tobacco cigarette smoking. Methods: We divided ever-tobacco smoking participants in the SubPopulations and InteRmediate Outcomes In COPD Study (SPIROMICS) into 3 groups based on self-reported marijuana use: current, former, or never marijuana smokers (CMSs, FMSs or NMSs, respectively). Longitudinal data were analyzed in participants with ≥2 visits over a period of ≥52 weeks. Measurements: We compared CMSs, FMSs, and NMSs, and those with varying amounts of lifetime marijuana use. Mixed effects linear regression models were used to analyze changes in spirometry, symptoms, health status, and radiographic metrics; zero-inflated negative binomial models were used for exacerbation rates. All models were adjusted for age, sex, race, baseline tobacco smoking amount, and forced expiratory volume in 1 second (FEV1) %predicted. Results: Most participants were followed for ≥4 years. Annual rates of change in FEV1, incident COPD, respiratory symptoms, health status, radiographic extent of emphysema or air trapping, and total or severe exacerbations were not different between CMSs or FMSs versus NMSs or between those with any lifetime amount of marijuana use versus NMSs. Conclusions: Among SPIROMICS participants with or without COPD, neither former nor current marijuana smoking of any lifetime amount was associated with evidence of COPD progression or its development. Because of our study's limitations, these findings underscore the need for further studies to better understand longer-term effects of marijuana smoking in COPD.